心肌梗死后，血管紧张素阻断通过信号转导和转录激活因子3（STAT3）抑制小而快反应细胞（SIF）DNA结合活性。

Angiotensin blockade inhibits SIF DNA binding activities via STAT3 after myocardial infarction.

作者信息

Omura T, Yoshiyama M, Takeuchi K, Kim S, Iwao H, Yamagishi H, Toda I, Teragaki M, Akioka K, Yoshikawa J

机构信息

First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.

出版信息

J Mol Cell Cardiol. 2000 Jan;32(1):23-33. doi: 10.1006/jmcc.1999.1051.

DOI:10.1006/jmcc.1999.1051

PMID:10652187

Abstract

The in vivo activation of transcription factors, which is important for cell regulation by gene expression, has not been well examined in myocardial infarcted heart. The purpose of this study was to determine whether myocardial signal transducer and activator of transcription (STAT) pathway is activated as sis-inducing factor (SIF) in infarcted heart, and to assess the angiotensin blockade on SIF activity in ischemic and non-ischemic myocardium of rat. Myocardial infarction was made by ligation of the coronary artery in Wistar rats. In electrophoretic mobility shift assay, myocardial SIF DNA binding activities gradually increased and reached to peak at 1 week in infarcted and non-infarcted regions after myocardial infarction. Imidapril and candesartan cilexitil significantly prevented the increase in SIF DNA binding activity in infarcted and non-infarcted regions. This increased SIF DNA complex was supershifted by specific anti-STAT3 antibody, indicating that increased SIF complex at least contained activated STAT3 proteins in myocardial infarcted heart. Furthermore, immunoprecipitation-Western blot analysis revealed that STAT3 of infarcted and non-infarcted regions were tyrosine-phosphorylated at 1 week after myocardial infarction. Imidapril and candesartan cilexitil prevented the increase in phosphorylated STAT3. Thus, the transcriptional activation of STAT3 through AT1 receptor may be partially involved in cardiac remodeling after myocardial infarction.

摘要

转录因子的体内激活对通过基因表达进行细胞调节很重要，但其在心肌梗死心脏中的研究尚不充分。本研究旨在确定心肌信号转导子与转录激活子（STAT）通路在梗死心脏中是否作为sis诱导因子（SIF）被激活，并评估血管紧张素阻断对大鼠缺血和非缺血心肌中SIF活性的影响。通过结扎Wistar大鼠冠状动脉制备心肌梗死模型。在电泳迁移率变动分析中，心肌梗死和未梗死区域的心肌SIF DNA结合活性在心肌梗死后逐渐增加，并在1周时达到峰值。咪达普利和坎地沙坦酯显著抑制梗死和未梗死区域SIF DNA结合活性的增加。这种增加的SIF DNA复合物被特异性抗STAT3抗体超迁移，表明梗死心脏中增加的SIF复合物至少包含活化的STAT3蛋白。此外，免疫沉淀-蛋白质印迹分析显示，心肌梗死后1周，梗死和未梗死区域的STAT3酪氨酸磷酸化。咪达普利和坎地沙坦酯抑制磷酸化STAT3的增加。因此，通过AT1受体对STAT3的转录激活可能部分参与心肌梗死后的心脏重塑。